维基百科

毕索洛尔

毕索洛尔（INN：bisoprolol）以Zebeta、Concor（康肯）等商品名于市面上贩售，是一种β受体阻滞剂，对β1肾上腺素受体（英语：beta-1 adrenergic receptor）具选择性，[7]用于治疗心血管疾病[7]（包括心跳过速、高血压、心绞痛和心脏衰竭[7] [8]）。此药物系透过口服方式给药。[7]

毕索洛尔
临床资料
商品名（英语：Drug nomenclature）Zebeta、Monocor及其他
AHFS/Drugs.comMonograph
MedlinePlusa693024
怀孕分级
  • 澳: C
给药途径口服给药
ATC码
法律规范状态
法律规范
药物动力学数据
生物利用度>90%
血浆蛋白结合率30%[4]
药物代谢50% 肝脏, 及酵素CYP2D6和CYP3A4[6]
生物半衰期10–12小时[5]
排泄途径肾脏, 粪便 (<2%)
识别信息
  • (RS)-14-[(2-Isopropoxyethoxy)methyl]phenoxy
    3-(isopropylamino)propan-2-ol
CAS号66722-44-9  checkY
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard（英语：CompTox Chemicals Dashboard） (EPA)
ECHA InfoCard100.108.941 编辑维基数据链接
化学信息
化学式C18H31NO4
摩尔质量325.45 g·mol−1
3D模型（JSmol（英语：JSmol））
手性外消旋体
  • O(c1ccc(cc1)COCCOC(C)C)CC(O)CNC(C)C
  • InChI=1S/C18H31NO4/c1-14(2)19-11-17(20)13-23-18-7-5-16(6-8-18)12-21-9-10-22-15(3)4/h5-8,14-15,17,19-20H,9-13H2,1-4H3 checkY
  • Key:VHYCDWMUTMEGQY-UHFFFAOYSA-N checkY

使用后常见的副作用有头痛、疲倦、腹泻和腿部肿胀。[7]较严重的副作用有气喘恶化、遮蔽辨识低血糖的能力以及心脏衰竭恶化。 [9]尚有个体于怀孕期间使用可能会对胎儿有害的疑虑。[10]

毕索洛尔于1976年取得专利，并于1986年获得瑞典批准用于医疗用途。[11]于1992年获得美国食品药物管理局（FDA）批准用作医疗用途。[7]

此药物已列入世界卫生组织基本药物标准清单之中。[12]市面上有通用名药物贩售。[7][13]美国于2020年中最常使用的处方药中，此药物排名第267，开立的处方笺数量超过100万张。[14][15]

医疗用途

 
商品名为Zebeta的毕索洛尔片剂，每片剂量5毫克。

毕索洛尔可用于预防心脏病发作后，有疾病恶化风险的患者再度发生心血管事件、[16]用于治疗郁血性心脏衰竭导致的射血分数降低[17]以及作为治疗高血压的二线药物。 [18]

毕索洛尔可能有治疗高血压的功效，但不建议作为一线药物。对于伴有合并症（例如郁血性心脏衰竭）的患者，它可作为一线抗高血压药物的辅助药物，对于已服用适当剂量的血管张力素转化酶抑制剂，但仍存在轻度至中度症状的患者，可添加此种β受体阻滞剂以促进疗效。[19]

该药物在心脏缺血（英语：Coronary ischemia）时可减少心肌的活动，而减少对氧气和营养的需求，并在血液供应较少的情况之下仍能输送足够量的氧气和营养以满足心脏的需求。[20][21][22]

副作用

过量使用可导致疲劳、低血压、[21]低血糖、[23][24]支气管痉挛和心跳过缓。发生支气管痉挛和低血糖是因为体内有高浓度药物时，可成为位于肺部和肝脏的β2肾上腺素受体（英语：β2 adrenergic receptor）的拮抗剂。支气管痉挛是由于肺部β2受体受到阻滞而发生。低血糖是由于肝脏中透过β2受体对肝糖分解和糖质新生的刺激减少而发生。[20][21][25]

目前尚无此药物造成相关临床明显药物性肝损伤的病例报告。[26]

注意事项

罹患气喘或支气管痉挛的个体应避免使用非选择性β受体阻滞剂，因为它们可能会引发恶化和症状加剧。[27][28][29]选择性β1肾上腺素受体阻断剂（如毕索洛尔）尚未显示会导致气喘恶化，[28]对于患有心脏合并症的轻至中度气喘，而已得到控制的患者可谨慎使用。

于2014年所做的一项统合分析发现，β1肾上腺受体选择性阻滞剂（毕索洛尔）对肺功能影响很小（与非选择性β受体阻滞剂比较），患者仍对沙丁胺醇（β2肾上腺素受体激动药）救援治疗产生反应，并赞同于选定有气喘，但已受控制的患者使用毕索洛尔。 [27][30]于2020年所做的一项临床试验支持前述观点，使用毕索洛尔对个体在沙丁胺醇给药后，不会对支气管扩张发生显著影响。 [31]

药理学

作用机转

毕索洛尔具有心脏保护作用，因为它能选择性、竞争性阻断儿茶酚胺（肾上腺素）对β1受体（肾上腺素受体）的刺激，β1受体主要存于心肌细胞和心脏电传导系统（心脏特有）中，但也存于肾脏的邻肾小球细胞中。[20]通常肾上腺素和正肾上腺素对β1受体的刺激会活化讯息传递级联，最终分别导致心肌收缩力（英语：Myocardial contractility）增加以及心肌和心脏起搏功能增强。[32]毕索洛尔会竞争性地阻断该级联反应的活化，因此降低心肌和心脏起搏细胞的肾上腺素活性/刺激。降低的肾上腺素活性表现为心肌收缩力减弱和心率降低。[23][24][33]

β1受体选择性

毕索洛尔的β1肾上腺素受体选择性在与其他非选择性β肾上腺素受体阻滞剂相比时尤为重要。此药物的作用仅限于含有β1肾上腺素受体的区域，主要是心脏和部分的肾脏。[23][33]虽然β1肾上腺素受体选择性药物（如毕索洛尔）可帮助患者避免某些与非选择性β受体阻滞剂活性相关的副作用[5]（作用于其他额外的肾上腺素受体，例如α1和β2），但并不表示它在治疗β受体阻滞剂适用心脏疾病（例如心脏衰竭）方面更具优势，但对于患有特定合并症的患者可能会有益处。[34][35]

毕索洛尔比阿替洛尔、美托洛尔和倍他洛尔（英语：betaxolol）具有更高程度的β1肾上腺素受体选择性。[36]此药物对β1受体的选择性比对β2受体的高出11至15倍。[33][37][38][39][40][41][42][43][44][45]另一种β受体阻滞剂奈必洛尔（英语：nebivolol）的β1受体选择性则约为高出3.5倍。[46][47]

肾素-血管张力素系统

毕索洛尔可抑制肾素（也称血管收缩素原酶）分泌约达65%，可抑制心搏过速约达30%。[37]

药物动力学

进入人体的毕索洛尔，其生物利用度高达约90%，生物半衰期为10-12小时。[23][24]循环中的毕索洛尔一半由肝脏代谢，其馀的以原有形式经肾脏排出，约少于2%可能经由粪便排出。[23][24][33]

毕索洛尔可溶于脂质和水。[23][33]它被归类为具有中等亲脂性的β受体阻滞剂，因此具有中等穿越血脑屏障的潜力。[48]因而毕索洛尔与高亲脂性β受体阻滞剂如普萘洛尔相比，可能会对中枢神经系统产生较小的的影响，且产生神经精神（英语：Neuropsychiatry）副作用的风险较低，相对而言，毕索洛尔比低亲脂性β受体阻滞剂如阿替洛尔所产生的影响会较较大。[48]

毕索洛尔与血浆蛋白结合率约为35%，分布容积为3.5升/公斤，总清除率约15升/小时 。毕索洛尔经两种方式从人体排除 - 50%在肝脏中转化为无活性的代谢物，然后经肾脏排泄。其馀50%则经由肾脏以药物原形排除。[49]由于肝脏和肾脏的消除相同，因此肝或是肾功能不全的患者无需调整剂量。

此药物的药物代谢动力学呈线性，且与年龄无关。[5]

在各项研究中，发现慢性心脏衰竭患者血浆中毕索洛尔的浓度高于健康受试者，生物半衰期也较长。目前尚缺乏此药物于健康受试者和慢性心脏衰竭受试者之间的药物代谢动力学直接比较证据。[50][51]

社会与文化

品牌名称

此药物在印度以Bisotab品牌销售。[52]于市面上的其他品牌尚有Cardicor, Congescor[53]及Bisoprolol-ratiopharm[54]等。

参考文献

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